Correlation of vaccine‐elicited antibody levels and neutralizing activities against SARS‐CoV‐2 and its variants

Jinbiao Liu; Brittany H Bodnar; Nigam H Padhiar; Adil I Khan; Fengzhen Meng; Sami Saribas; Peng Wang; Xu Wang; Elizabeth McCluskey; Sahil Shah; Huaqing Zhao; Jin Jun Luo; Wen‐Hui Hu; Wen‐Zhe Ho

摘要

Dear Editor, The COVID‐19 vaccines (Pfizer‐BNT162b2 and Moderna‐mRNA‐1273) can elicit an effective immune response against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. ~(1) , ~(2) However, titers of elicited serum antibody to spike protein of the virus differ among vaccinated individuals and decline after vaccination. ~(3) , ~(4) Additionally, the ability of the vaccines to protect against newly emerged variants needs to be further elucidated. Therefore, it is important to understand the correlation between levels of vaccination‐induced antibody and neutralizing activity against SARS‐CoV‐2, including the variants. Previous authors have investigated the subject of vaccine efficacy against SARS‐CoV‐2 variants using both clinical and in‐vitro models. For example, a study by Bernal et?al. comparing the B.1.617.2 and B.1.1.7 variants using clinical data noted only modest differences in BNT162b2 and ChAdOx1 vaccine's effectiveness. ~(5) Abu‐Raddad et?al. used a similar test‐negative case‐control design and found that the BNT162b2 vaccine's effectiveness was reduced against B.1.351, but noted that protection against severe disease was still robust. ~(6) An in‐vitro study using BNT162b2‐elicited serum by Liu et?al. reported a roughly equivalent neutralization of B.1.1.7 and P.1 variants when compared to USA‐WA1/2020 and slightly lower (but still robust) neutralization for B.1.351. ~(7) Another in‐vitro study by Chen et?al. reported reductions in neutralizing activity against B.1.1.7 and B.1.351 variants when examining geometric mean titers (GMTs) using BNT162b2 derived serum. ~(8) Data from Stamatatos et?al. examining the neutralizing ability of sera from 15 donors vaccinated with either Pfizer/BioNTech BNT162b2 or Moderna mRNA‐1273 demonstrated that the two mRNA vaccines have reduced potency against divergent variants, specifically B.1.351. ~(9) In summary, these authors have noted decreased vaccine efficacy against the B.1.351 variant. However, few of these studies included a large cohort of Moderna mRNA‐1273 vaccinated donors, and fewer still attempted to compare the neutralizing ability of Moderna mRNA‐1273 elicited serum to BNT162b2 elicited serum when looking at both the Wuhan‐1 reference isolate and its variants. These prior studies also did not attempt to show any correlation between serum Immunoglobulin G (IgG) levels and neutralizing ability. We thus examined levels of vaccine‐elicited serum antibody and neutralizing activities against pseudoviruses bearing spike proteins from the original Wuhan‐1 reference isolate (wild type, WT) and the variants (D614G, UK‐B.1.1.7, UK‐B.1.525 and SA‐B.1.351) (Table S1 ). We obtained sera samples from 30 mRNA‐BNT162b2 (Pfizer) vaccinated subjects (22–68 days after 2nd dose) and 19 mRNA‐1237 (Moderna) vaccinated subjects (24–49 days after 2nd dose) (Table S2 ). This study was approved by Temple University Institutional Review Board (IRB; IRB #28021) and the informed consent forms were signed by all study subjects. We measured the serum titers of specific IgG antibodies to SARS‐CoV‐2 spike S1 by an enzyme‐linked immunosorbent assay and demonstrated that all subjects vaccinated with either Pfizer or Moderna vaccine had detectable levels of serum IgG. The Pfizer group IgG titers ranged from 1.05?×?10 ~(4) to 1.68?×?10 ~(5)?ng/ml, and the Moderna group IgG titers ranged from 2.01?×?10 ~(4) to 1.70?×?10 ~(5)?ng/ml (Figure? 1A ). Given that the distribution of the IgG titers was left‐skewed (Figure? 1B ), we reported the GMTs, with the geometric standard deviation factor (GSDF) and the 95% CI of the GMT. For the Pfizer group, the GMT was 6.12?×?10 ~(4)?ng/ml (GSDF?=?2.24, 95% confidence interval [CI]?=?4.53?×?10 ~(4)–8.27?×?10 ~(4)?ng/ml). For the Moderna group, the GMT was 9.24?×?10 ~(4)?ng/ml (GSDF?=?1.90, 95% CI?=?6.78?×?10 ~(4)–1.26?×?10 ~(4)?ng/ml). The Wilcoxon rank‐sum test p ‐value comparing both groups’ IgG titers was 0.0906, and thus the difference in post‐vaccination titers between Pfizer and Moderna recipients was not statistically significant ( p ?&?0.05). FIGURE 1 Distribution of specific anti‐severe acute respiratory syndrome coronavirus 2 (anti‐SARS‐CoV‐2) S1 Immunoglobulin G (IgG) in serum from vaccine recipients and distribution of ID _(50) values for each variant. (A) Shown is specific anti‐SARS‐CoV‐2 S1 IgG in sera collected from Pfizer ( N ?=?30) and Moderna ( N ?=?19) vaccinated subjects approximately 3?weeks to 2 months after the second dose of vaccination. A Wilcoxon rank‐sum test was used for the p ‐value calculation. (B) Shown is the distribution of all of the serum IgG titers from 49 donors. (C) Shown is 50% pseudovirus neutralization titer (50% inhibitory dilution, ID _(50)) against recombinant vesicular stomatitis virus‐based SARS‐CoV‐2 pseudovirus bearing the Wuhan‐1 (wild type, WT) spike protein in sera collected from Pfizer and Moderna vaccinated subjects. Box plots indicate the median and interquartile range (I

机译：亲爱的编辑器，Covid-19疫苗（PFizer-BNT162B2和Moderna-mRNA-1273）可以针对严重急性呼吸综合征冠状病毒2（SARS-COV-2）感染有效的免疫应答。〜（1），〜（2）然而，引发的血清抗体对病毒的尖峰蛋白的滴度不同，疫苗接种后的疫苗接种的个体和下降。〜（3），〜（4）另外，需要进一步阐明疫苗防止新出现的变体的能力。因此，重要的是要理解疫苗接种诱导的抗体水平与SARS-COV-2的中和活性之间的相关性，包括变体。以前的作者使用临床和体外模型研究了针对SARS-COV-2变体的疫苗疗效的主题。例如，Bernal et？al的研究。比较B.1.617.2和B.1.1.7使用临床数据的变体仅注意到BNT162B2和Chadox1疫苗的有效性的适度差异。〜（5）ABU-RADDAD等等。使用了类似的测试负案例控制设计，发现BNT162B2疫苗的有效性降低了B.1.351，但指出对严重疾病的保护仍然是稳健的。〜（6）使用Liu等，使用BNT162B2引发血清的体外研究。报告与USA-WA1 / 2020相比，B.1.1.7和P.1变体的大致等同的中和。与B.1.351的略低（但仍然稳健）中和略低（但仍然稳健）。〜（7）Chen Et？Al的另一个体外研究。报告使用BNT162B2衍生的血清检查几何平均滴度（GMTS）时对B.1.1.7和B.1.351变体的中和活动的降低。〜（8）Stamatatos等的数据吗？检查血清的中和能力从用辉瑞/ Biontech BNT162B2或UndioNA mRNA-1273接种接种疫苗的供体表明，两个mRNA疫苗对发散变体的效力降低，特别是B.1.351。〜（9）总之，这些作者指出，对B.1.351变体的疫苗疗效降低。然而，这些研究中的很少包括大量的现代MRNA-1273接种疫苗的捐赠者，并且在观察武汉-1参考分离物和其时，仍然试图比较现代MRNA-1273引发血清的中和能力。变体。这些目前的研究也没有试图在血清免疫球蛋白G（IgG）水平和中和能力之间表现出任何相关性。因此，我们检查了来自原始武汉-1参考分离株（野生型，WT）和变体的刺激素蛋白的疫苗引发血清抗体和对副病毒的中和活性的中和活性（D614G，UK-B.1.1.7，UK-B。 1.525和SA-B.1.351）（表S1）。我们从30 mRNA-BNT162B2（辉水剂）接种受试者（2〜68天后22-68天）的血清样品和19 mRNA-1237（现代）疫苗受试者（第2剂后24-49天）（表S2）。本研究经寺院大学机构审查委员会批准（IRB; IRB＃28021），所有研究科目签署了知情同意书。通过酶联免疫吸附测定法测定了特定IgG抗体的血清滴度，并通过酶联免疫吸附测定测定了SARS-COV-2峰值S1，并证明所有受磷染色剂或现代疫苗接种的受试者可检测到血清IgG水平。辉瑞组IgG滴度范围为1.05？×10〜（4）至1.68？×10〜（5）？ng / ml，和现代群IgG滴度从2.01？×10〜（4）到1.70 ？×10〜（5）？ng / ml（图？1a）。鉴于IgG滴度的分布是留下的（图？1B），我们报告了GMT，具有几何标准偏差因子（GSDF）和GMT的95％CI。对于辉瑞组，GMT为6.12？×10〜（4）？Ng / ml（GSDF？=？2.24,95％置信区间[CI]？=？4.53？×10〜（4）-8.27？ ×10〜（4）？ng / ml）。对于现代群体，GMT为9.24？×10〜（4）？ng / ml（GSDF？=？1.90,95％CI？=？6.78？×10〜（4）-1.26？×10〜（4）？ng / ml）。比较两组IgG滴度的Wilcoxon Rank-Sum试验P -Value为0.0906，因此辉瑞和现代接受者之间的接种后滴度的差异在统计学上没有统计学意义（P？＆amp; ？0.05）。图1从疫苗接受者的血清中血清中血清特异性抗重度呼吸综合征冠状病毒2（抗SARS-COV-2）S1免疫球蛋白G（IgG）的分布和每个变体的ID _（50）值的分布。（a）所示是从辉瑞（n？=Δ30）和现代疫苗接种的血清中收集的血清中的特异性抗SARS-COV-2 S1 IgG约3？疫苗的受试者在第二剂后约3个月至2个月疫苗接种。用于P-value计算的Wilcoxon Rank-Sum试验。（b）所示是来自49个供体的所有血清IgG滴度的分布。（c）所示是对血清中武汉-1（野生型，WT）穗蛋白的基于重组囊泡口炎病毒的SAR-COV-2假病毒（50％抑制稀释，ID稀释，ID _（50））的抑制滴度为50％从辉瑞和现代疫苗接种的科目中收集。盒子图表示中位数和侧链范围（I

Correlation of vaccine‐elicited antibody levels and neutralizing activities against SARS‐CoV‐2 and its variants

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